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Research Article

Inflammation, Insulin Resistance, and Diabetes—Mendelian Randomization Using CRP Haplotypes Points Upstream

  • Eric J Brunner mail,

    To whom correspondence should be addressed. E-mail: e.brunner@ucl.ac.uk

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Mika Kivimäki,

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Daniel R Witte,

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Debbie A Lawlor,

    Affiliation: Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom

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  • George Davey Smith,

    Affiliation: Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom

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  • Jackie A Cooper,

    Affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, United Kingdom

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  • Michelle Miller,

    Affiliation: Clinical Sciences Research Institute, Warwick Medical School, Coventry, United Kingdom

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  • Gordon D. O Lowe,

    Affiliation: Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom

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  • Ann Rumley,

    Affiliation: Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom

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  • Juan P Casas,

    Affiliation: Non-communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom

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  • Tina Shah,

    Affiliation: University College London Centre for Clinical Pharmacology, Division of Medicine, London, United Kingdom

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  • Steve E Humphries,

    Affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, United Kingdom

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  • Aroon D Hingorani,

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Michael G Marmot,

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Nicholas J Timpson,

    Affiliation: Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom

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  • Meena Kumari

    Affiliation: Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom

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  • Published: August 12, 2008
  • DOI: 10.1371/journal.pmed.0050155

About the Authors

Eric J Brunner, Mika Kivimäki, Daniel R Witte, Aroon D Hingorani, Michael G Marmot, Meena Kumari
Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, United Kingdom
Debbie A Lawlor, George Davey Smith, Nicholas J Timpson
Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom
Jackie A Cooper, Steve E Humphries
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, United Kingdom
Michelle Miller
Clinical Sciences Research Institute, Warwick Medical School, Coventry, United Kingdom
Gordon D. O Lowe, Ann Rumley
Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom
Juan P Casas
Non-communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom
Tina Shah
University College London Centre for Clinical Pharmacology, Division of Medicine, London, United Kingdom

Corresponding Author

Email: e.brunner@ucl.ac.uk

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

EJB, M. Kivimäki, DAL, MM, SEH, ADH, and M. Kumari designed the study. EJB, JAC, and MM analyzed the data. MM, GDOL, AR, TS, MGM, and M. Kumari collected data or did experiments for the study. EJB and M Kivimäki wrote the first draft of the paper. EJB, M. Kivimäki, DRW, DAL, GDS, JAC, MM, GDOL, AR, JPC, ADH, MGM, NJT, and M. Kumari contributed to writing the paper. M. Kivimäki helped in conducting the data analysis and interpretation. DRW contributed to the analysis of the data. MM supervised (scientific and administrative roles) the DNA extraction program and genotyping and was responsible for checking genotype results and in particular for verifying concordance of blind duplicates, establishing error rates, etc. GDOL supervised laboratory assays. TS selected CRP tag SNPs and conducted genotyping of these SNPs. NJT helped with analysis.